The built environment correlates of objectively measured physical activity in Norwegian adults:A cross-sectional study

Background: Built environments that are designed to provide accessible, attractive, and convenient locales promote regular physical activity(PA).Norway has great variability in its geographic, natural, and built environment features. Urban areas have well-developed built environment features, whereas the rural areas are less walkable and this may influence the mode of transport. In general, active transport is more common in urban centers. Further, public transportation is more developed in urban areas, whereas motorized transport may be more widespread in the rural areas. Despite this, in Sogn & Fjordane, a rural county in western Norway, high PA levels are frequently observed. Thus, the aims of this study were to(1) explore perceived built environment features and characterize their associations with objectively measured PA levels in Norwegian adults and(2) explore the differences in these correlates between Sogn & Fjordane and the rest of Norway.Methods: In this cross-sectional study, participants used questionnaires to rate perceptions of their built environments, and their PA was objectively measured for 7 consecutive days using the Acti Graph GT1 M accelerometer. There were 972 Norwegian adults who were included in the study. The average age was 46.9 ± 6.5 years and 43.8% of participants were men. Data were analyzed using multiple linear regression.Results: Total PA and moderate-to-vigorous physical activity(MVPA) were both associated with perceived walkability, the community perception score, and active transport for commuting(all p ≤ 0.004). We also observed geographic-area-specific associations: the community perception score was negatively associated with total PA and MVPA in the rest of Norway(p ≤ 0.012) but not in Sogn & Fjordane. Public transport for commuting was positively associated with MVPA in Sogn & Fjordane(p = 0.03) but not in the rest of Norway.Conclusion: Total PA level and MVPA were associated with built environment factors, such as perceptions of community, perceived walkability,and engaging in active transport for commuting. Geographic differences in the PA correlates were observed, and thus, locally customized environmental population approaches aimed at increasing PA levels may be essential complements to individual behavior and lifestyle strategies.Further, objective measures of Norwegian built environments, such as geographic information system data, and validated walk-and bike-scores would advance the field.

Insights into the Use of CDK 4/6 Inhibitors in Patients with HR-positive Advanced or Metastatic Breast Cancer

Hormone receptor(HR)-positive breast cancer(BC)is the most common subtype of BC and some patients with such tumors experience recurrences.Endocrine-based therapy(ET)(e.g.,tamoxifen,aromatase inhibitors(AIs),and fulvestrant)that has improved outcomes in such patients represents the initial therapy for women with HR-positive/human epidermal growth factor receptor 2(HER2)-negative BC(considering no evidence of visceral crisis).However,the resistance to ET can occur in almost 50%of HR-positive BCs.In order to improve outcomes of patients with HR-positive metastatic BC,new treatment strategies are required.One such therapy is the new class of medications,cyclin-dependent kinase(CDK)4/6 inhibitors,that have improved the outcomes in such patients(both endocrine-sensitive and endocrine-resistant).This article presents evidence from the main clinical trials,which led to the approval of palbociclib,ribociclib,and abemaciclib.These three CDK 4/6 inhibitors have shown a significant improvement of the progression-free survival(PFS)in patients with HR-positive/HER2-negative metastatic BC when used in combination with selected ETs.In addition,some important patient management considerations,when choosing a particular CDK 4/6 inhibitor for an individual patient are presented.Furthermore,a need to find biomarkers for CDK 4/6 inhibitor sensitivity,efficacy,and resistance,to be able to precisely select the best patientcandidates for this treatment is highlighted.

Perspectives on endogenous and exogenous tissue engineering following injury to tissues of the knee

The knee is a multi-component organ system comprised of several tissues which function coordinately to provide mobility. Injury to any one component compromises the integrity of the system and leads to adaptation of the other components. Over time, such events often lead to dysfunction and degeneration of the knee. Therefore, there has been considerable research emphasis to repair injured components in the knee including cartilage, menisci, and ligaments. Approaches to improving healing and repair/regeneration of knee tissues have included surgery, anti-sense gene therapy, injection of growth factors and inflammatory cytokine antagonists, transplantation of in vitro expanded chondrocytes, enhancement of endogenous cells via microfracture, injection of mesenchymal stem cells, and implantation of in vitro tissue engineered constructs. Some of these approaches have lead to temporary improvement in knee functioning, while others offer the potential to restore function and tissue integrity for longer periods of time. This article will review the status of many of these approaches, and provide a perspective on their limitations and potential to contribute to restoration of knee function across the lifespan.

Human Heterogeneity and Survival of the Species: How Did It Arise and Being Sustained?—The Conundrum Facing Researchers

Current humans, Homo sapiens, are genetically and epigenetically very heterogeneous, and subsequently also biologically and physiologically heterogeneous. Much of this heterogeneity likely arose during evolutionary processes, via various iterations of humanoid lineages, and interbreeding. While advantageous from a species perspective, the heterogeneity of humans poses serious challenges to researchers attempting to understand complex disease processes. While the use of inbred preclinical models makes the research effort more effective at some levels, the findings are often not translatable to the more heterogeneous human populations. This conundrum leads to considerable research activity with inbred preclinical models, but modest progress in understanding many complex human conditions and diseases. This article discusses several of the issues around human heterogeneity and the need to change some directions in preclinical model research. Using newer Artificial Intelligence and Machine Learning approaches can begin to deduce important elements from the complexity of human heterogeneity.

A better parameter in predicting insulin resistance:Obesity plus elevated alanine aminotransferase

AIM:To investigate the association of obesity and elevated alanine aminotransferase with insulin resistance and compare these factors with metabolic syndrome. METHODS:We enrolled a total of 1308 male workers aged from 22 to 63 years.Data was extracted from the workers'periodic health check-ups in hospitals.All cases were from the community of northern Taiwan. This was a cross-sectional observational study from July to September in 2004.We grouped all cases into four groups,based on the quartile of homeostasis model assessment.The top fourth quartile group was defined as the group with insulin resistance.We performed multivariate logistic regression analysis for the odds ratio of the risk factors for insulin resistance. RESULTS:Compared with metabolic syndrome,the coexistence of both factors had a 4.3-fold(95%CI: 2.7-6.8)increased risk,which was more than metabolic syndrome with a 3.6-fold(95%CI:2.6-5.0)increased risk.The two factors had a synergistic effect.The synergistic index of obesity and elevated alanine aminotransferase(ALT)was 2.1(95%CI:1.01-4.3).CONCLUSION:Obesity and elevated ALT are associatedwith insulin resistance.The effects are synergistic. Coexistence of them is better than metabolic syndrome in predicting insulin resistance.

Colonic mucosa-associated lymphoid tissue lymphoma identified by chromoendoscopy

Colonic mucosa-associated lymphoid tissue(MALT)lymphomas are a rare occurrence and the definitive treatment has not been established.Solitary or multiple,elevated or polypoid lesions are the usual appearances of MALT lymphoma in the large intestine and sometimes the surface may reveal abnormal vascularity.Herein,we report a case of MALT lymphoma and review the relevant literature.Upon colonoscopy,a suspected pathologic lesion was observed in the proximal transverse colon.The lesion could be distinguished more prominently after using narrowband imaging mode and indigo carmine-dye spraying chromoendoscopy.Histopathologic examination of this biopsy specimen revealed lymphoepithelial lesions with diffuse proliferation of atypical lymphoid cells effacing the glandular architecture and centrocyte-like cellsinfiltrating the lamina propria.Immunohistochemical analyses showed that tumor cells were positive for CD20 and Bcl-2e,and negative for CD10,CD23,and Bcl-6.According to Ann-Arbor staging system,the patient had stage IIE.A partial colectomy with dissection of the paracolic lymph nodes was performed.Until now,there is no recurrence of lymphoma at follow-up.

Interrelations Between Psychological Stress and Cancer-Deciphering Molecular Signals in the Tumor Microenvironment

Current research has revealed some links between psychological stress and cellular mutation,neoplastic proliferation and metastasis in patients with cancer.In stressful situations,the stress-related neuroendocrine mediators(e.g.,catecholamines,and glucocorticoids(GSs))are being secreted,via stimulation of the sympathetic nervous system(SNS),and the hypothalamic-pituitaryadrenocortical(HPA)axis.Catecholamine may affect the malignant progression,since they can regulate various cellular signaling pathways,via adrenergic receptors(ARs)that are expressed by different types of neoplastic cells.The ARs increase the proliferation and invasive potential of such cells,and change their“behavior”in the tumor microenvironment.Similarly,cortisol and its glucocorticoid receptors(GRs)can promote stress-induced malignant growth and metastasis.Maladaptation to stressful situations,often relevant to the cancer diagnosis and treatment,may accelerate tumor growth and spread(e.g.,via inflammation,angiogenesis,and migration).Studies have shown that psychological interventions can be helpful for adaptation to adverse circumstances during the therapeutic process in patients with cancer.This mini-review will address some interrelations between psychological stress and cancer.It will discuss how the receptor-mediated signaling pathways may lead to cancer initiation,propagation,and spread.In addition,it will describe a supportive role of the stress reduction strategies,for example,in patients with breast cancer(BC).

Searching for Better Outcomes among Patients with Metastatic Triple- Negative Breast Cancer – Do We Have Novel Options on the Treatment Landscape?

Triple-negative breast cancer(TNBC),which accounts for approximately 15%of breast cancers(BCs)is characterized by a lack of expression of the hormone receptors(HRs)(estrogen receptor(ER)and progesterone receptor(PR)),and human epidermal growth factor receptor 2(HER2).TNBC reveals very aggressive behavior and often leads to poor prognosis.Unfortunately,standard chemotherapy(CHT)is related to low response rates and short progression-free survival(PFS)in patients with metastatic TNBC,creating an unmet need.However,recent recognition of different molecular subtypes and mutations within TNBC has allowed exploring some innovative targeted therapies,bringing new hope for women suffering from TNBC.Currently,some promising systemic treatment options in this area have been developed,including targeted therapies,such as poly(ADP-ribose)polymerase(PARP)inhibitors,immune checkpoint inhibitors,antibody-drug conjugates,and AKT inhibitors.The aim of this mini-review is to address these novel treatment modalities and highlight the main directions for further research and clinical practice in the advanced or metastatic forms of TNBC.This article presents poly(ADP-ribose)polymerase(PARP)inhibitors(e.g.,olaparib,talazoparib,and valaparib for treatment of BRCA-mutated,HER2-negative metastatic BC),immune checkpoint inhibitors(atezolizumab and pembrolizumab),an antibody-drug conjugate(ADC)(sacituzumab govitecan),and AKT inhibitors(ipatasertib and capivasertib).A brief outline of the main clinical trials leading to the approval of these new medications has been provided.Moreover,this overview discusses the efficacy and safety of these innovative treatment options,focusing on women with metastatic TNBC.In addition,this paper comments on some recent considerations,regarding avenues of delivering care and conduct clinical trials in patients with BC,during the COVID-19 pandemic.

Combination of high-sensitivity C-reactive protein and homocysteine may predict an increased risk of coronary artery disease in Korean population

Background The association of emerging biomarkers such as high-sensitivity C-reactive protein （hs-CRP）,homocysteine and fibrinogen with the risk of coronary artery disease （CAD） is still uncertain in Asian population including Koreans and little is known about the combined effect of biomarkers on the risk of CAD.Methods A total of 10 650 subjects （6538 men and 4112 women） were enrolled in this study.A 10-year CAD risk was calculated using Framingham risk score modified by the National Cholesterol Education Program （NCEP） Adult Treatment Panel Ⅲ （ATP Ⅲ ） and levels of circulating hs-CRP,homocysteine and fibrinogen were measured using validated assays.Results The 10-year CAD risk gradually augmented with increase in the circulating levels of hs-CRP,homocysteine and fibrinogen.For the highest quartile of hs-CRP,odds ratio （OR） of high-risk for CAD （10-year risk ≥20%） compared with the lowest quartile was 3.97 （95% C/：2.51-6.29）.For homocysteine and fibrinogen,ORs in the highest quartile compared to the lowest quartile were 5.10 （95% Cl：3.05-8.53,P 〈0.001） and 1.46 （95% Cl：0.69-3.11,P=0.325）,respectively.OR of high-risk for CAD in both the highest quartile of hs-CRP and homocysteine was 9.05 （95% CI：5.30-15.45） compared with the below median of hs-CRP and homocysteine.Conclusions The present study demonstrated that hs-CRP and homocysteine are well associated with the 10-year CAD risk estimated using NCEP ATP Ⅲ in Koreans and combination of hs-CRP and homocysteine can have strong synergyin predicting the development of CAD.

Relationship of plasminogen activator inhibitor 1 gene 4G/5G polymorphisms to hypertension in Korean women

Background Hypertension （HTN） is a major determinant of various cardiovascular events. Plasma levels of plasminogen activator inhibitor 1 （PAl-l） modulate this risk. A deletion/insertion polymorphism within the PAl-1 loci （4G/4G, 4G/5G, 5G/5G） affects the expression of this gene. The present study investigated the association between PAl-1 loci polymorphisms and HTN in Korean women. Methods Korean women （n=1312） were enrolled in this study to evaluate the association between PAl-1 4G/5G gene polymorphisms and HTN as well as other metabolic risk factors. PAl-1 loci polymorphisms were investigated using polymerase chain reaction amplification and single-strand conformation polymorphism analysis. Results The three genotype groups differed with respect to systolic blood pressure （P=0.043）, and diastolic blood pressure （P=0.009） but not with respect to age, body mass index, total cholesterol, low or high density lipoprotein cholesterol, triglycerides, or fasting blood glucose. Carriers of the PAl-1 4G allele had more hypertension significantly （PAl-1 4G/5G vs. PAl-1 5G/5G, P=0.032; PAl-1 4G/4G vs. PAl-1 5G/5G, P=0.034）. When stratified according to PAl-1 4G/5G polymorphism, there was no significant difference in all metabolic parameters among PAl-1 genotype groups in patients with HTN as well as subjects with normal blood pressure. The estimated odds ratio of the 4G/4G genotype and 4G/5G for HTN was 1.7 （P=0.005）, and 1.6 （P=0.015）, respectively. Conclusion These findings might indicate that PAl-1 loci polymorphisms independently contribute to HTN and that gene-environmental interaction may be not associated in Korean women.

Serum Gamma-glutamyl Transferase Concentration Within the Reference Range is Related to the Coronary Heart Disease Risk Prediction in Korean Men： Analysis of the Korea National Health and Nutrition Examination Survey （V-1, 2010 and V-2, 2011）

Background：Limited data exist on the association of serum gamma-glutamyl transferase （GGT） level within the reference range with the increased risk of coronary heart disease （CHD） prediction in men.The study examined the association between serum GGT concentration within the reference range and the CHD risk prediction in Korean men.Methods：The study employed data from Korean National Health and Nutrition Examination Survey （V-1,2010 and V-2,2011） where a total of 1301 individuals were analyzed.A 10-year CHD risk prediction was computed using the Framingham Risk Score （FRS） modified by the National Cholesterol Education Program （NCEP） Adult Treatment Panel Ⅲ （ATP Ⅲ）.Results：Positive correlations were established between log-transformed GGT concentration and FRS （r =0.237,P 〈 0.001）.After adjustment of body mass index,the amount of alcohol intake and low-density lipoprotein-cholesterol,the odds ratio （95% confidence interval） for intermediate risk and beyond of 10-year CHD prediction （10-year risk ≥10%） with lowest quartile of participants was 1.21 （0.78-1.87） for second quartiles,1.39 （0.88-2.21） for third quartiles and 2.03 （1.23-3.34） for highest quartiles.Conclusions：Higher serum GGT within its reference range was significantly correlated with a 10-year CHD risk prediction estimation using NCEP ATP Ⅲ in Korean men.

Comparison on colonoscopic parameters according to length of adult-colonoscope

Background High success rate of intubation and short intubation time have been needed to endoscopists for a complete and comfortable coolonoscopy,if possible.The purpose of present study was to compare procedure efficiencies according to adult-colonoscope length.Methods This was a prospective,randomized,single-blinded controlled trial.A total of 239 healthy Korean subjects were randomly assigned to two groups：one group receiving intermediate-length adult-colonoscope （n=119）,and the other group receiving long-length adult-colonoscope （n=120）.Cecal intubation time and rate,and terminal ileal intubation time and rate as well as other procedure-related outcomes （adenoma detection rate,withdrawal time,and total procedure time） were evaluated.Results There were significant differences in cecal intubation time and terminal ileal intubation rate according to colonoscope length.The time of cecal intubation was shorter in the intermediate-scope group than that in the long-scope group （（222.13±101.67） s vs.（253.85±109.40） s,P=-0.014）.However,the rate of terminal ileal intubation was higher in the long-scope group than that in the intermediate-scope group （94.2％ vs.83.2％,P=-0.007）.In addition,terminal ileal intubation time was also shorter in the long-scope group than that in the intermediate-scope group （（35.21±38.89） s vs.（44.09±33.87） s,P ＜0.001）.There were no significant differences in other procedure-related outcomes between the two groups.Conclusions The intermediate-length adult-colonoscope had an advantage over the long-length adult-colonoscope regarding cecal intubation time,whereas the long-scope had an advantage over the intermediate-scope regarding the rate and time of terminal ileal intubation.These results suggest that it is rational to prepare and use these two types of colonoscope properly,instead of employing only one type of colonoscope.

Efficacy and Safety of ＂URSA Complex＂ in Subjects with Physical Fatigue： A Multicenter, Randomized, Double-blind, Placebo-controlled Trial

Background： Fatigue is a common symptom both in diseases status and in healthy subjects. Various supplements and nutraceuticals for relieving of fatigue have been used. However, there are a few studies to evaluate the efficacy and the safety of the drug tbr fatigue alleviation, we conducted using URSA Complex to evaluate the efficacy on physical fatigue via score changes in the checklist individual strength （CIS）. Methods： The study was designed as a multicenter, randomized, double-blind, placebo-controlled trial, with subjects randomized to one of the two arms, receiving either placebo or URSA Complex administered as identical capsules. The primary efficacy endpoints of this clinical trials are the ratio of improving CIS scores 〈 76 points in patients at the end （4 weeks）. Secondary efficacy variables are as follows one is an improvement of fatigue and the other is an improvement of the liver enzyme. Results： The fatigue recovery rate in who had improved CIS scores of 〈 76 points were 70.0%, 50.9% in the therapy group and placebo group, respectively （P = 0.0l 9）. The fatigue recovery rate in CIS score was higher in URSA Complex therapy group than placebo group. The difference between therapy group and placebo group was statistically significant at 4 weeks later, but not 2 weeks. Conclusions： Our results provided that the URSA Complex was effective in alleviating physical fatigue. The adverse event frequency in the therapy groups was similar to that in the placebo group.

Assessment of muscle strength in para-athletes:A systematic review of observational studies

Accurate and reliable evaluation of muscle strength in para-athletes is essential for monitoring the effectiveness of strength training and/or rehabilitation programmes,and sport classification.Our aim is to synthesise evidence related to assessing muscle strength in para-athletes.Four databases were searched from January 1990 to July 2021 for observational studies focusing on strength assessment.Independent screening,data extraction,and quality assessment were performed in duplicate.A total of 1764 potential studies were identified.Thirty met the inclusion criteria and were included in the review.The mean age of participants was 30.7 years(standard deviation[SD]:2.4).The majority were men(88%)participating in wheelchair sports,including basketball,rugby,and tennis(23/30:76%).Overall quality varied,with more than half of the studies failing to identify strategies for dealing with confounding variables.Despite manual muscle testing being a standard component of para-sport classification systems,evidence examining strength characteristics in para-athletes is derived primarily from isometric and isokinetic testing.In studies that included comparative strength data,findings were mixed.Some studies found strength values were similar to or lower than able-bodied athletic controls.However,an important observation was that others reported higher shoulder strength in para-athletes taking part in wheelchair sports than both able-bodied and disabled non-athletes.Studies need to develop accessible,standardised strength testing methods that account for training influence and establish normative strength values in para-athletes.There is also a need for additional studies that include female para-athletes and para-athletes with greater functional impairments.

D-penicillamine-induced Elastosis Perforans Serpiginosa

To the Editor： Elastosis perforans serpiginosa （EPS） is part of different kinds of perforating diseases that are dependent on factors such as idiopathic, reactive, or drug induced. We report here a case of a patient who presented with multiple reddish-brown keratinized papules coalescing to form serpiginous plaques in the anterior and posterior of the neck, which was found to be typical D-penicillamine-induced EPS.

Candida Balanitis with Hyperplastic Plaque Mimicking Vascular Neoplasm

To the Editor：A 6 1-year-old diabetic male presented with a growing hyperplastic plaque measured 1.5 cm × 1.0 cm on the glans of his penis for 2 months [Figure l a].The plaque was pruritic burning.Polarized dermoscopy revealed multiple red papules with whitish areas of erosions [Figure 1 b].The patient was diagnosed as vascular neoplasm at other hospitals and he came to the Department of Dermatology,Peking University People＇s Hospital for further consultation before an excision surgery.